Malaria in pregnancy (MiP) is a serious public health problem which can be minimized by the use of Insecticides Treated Nets (ITNs) and Intermittent Preventive Treatment of malaria in pregnancy (IPTp). Inflammatory protein biomarker especially C-reactive protein and serum amyloid A can be used to detect MiP at subclinical level.A total of 547 pregnant women were screened from three Primary Health Centers (PHCs) Samaru, with 75Plasmodium falciparum positive. Malaria was diagnosed by both HRP2 (RDT) and Giemsa staining techniques, while socio-demographic data was obtained using semi-structured pretested questionnaires.Haemato-analyzer was used for Hb-concentration, leucocytes and platelets counts, while spectrophotometry was used for Iron, Zinc, Copper and Albumin estimations.ELISA technique was used for serum C-reactive protein, Amyloid A, Ferritin and Transferrin determinations. Results obtained showed 13.7% prevalence rate of P. falciparum infection.The peak age specific incidence was 15-19 years (17.5%), with mean parasite density of 5925. Those with no-formal education were affected mostly (17.4%) with parasite burden of 4419; while across occupation there was no difference in terms of infection rate and mean parasite density. Pregnant women were mostly predisposed to P. falciparum infection due to non-availability of ITNs, 41.3% of pregnant mothers had not use nets at all during pregnancy.Majority(68.3%) of the pregnant mothers complied with the use of IPTp, which may have led to reduced prevalence of P. falciparuminfection in the study area. Incidence of P. falciparum infection varied significantly according to gestation period and parity, 19.9% for first trimester with mean parasite density of 7644 and primigravidae(19.0%) with mean parasite density of 9764 respectively. Patients with malaria and concomitant iron deficiency anemia (IDA) had mean sTfR level of 7.7 ±0.26 ng/ml (0.1- 5.0ng/ml), and Ferritin level of 385.8±56.6(22.5-278.6)pmol/L. Soluble Transferrin in normal subjects and patients with P. falciparum malaria showed no significant difference (p > 0.05). Statistically significant difference (p < 0.001) was observed in patients with malaria and concomitant IDA as compared to normal control group. This results showed that estimation of changes in some Acute Phase Proteins (CRP and SAA), despite the lack of diagnostic specificity may be useful to clinicians because such changes reflect the presence and intensity of inflammatory process (malaria infection), as well as trace element metabolism during malaria infection. The cohabitation of parasite manifestation and nutritional deficiency of trace elements creates damage in the health of infected population, due alteration in Zn/Cu ratio.

1.1 Background Information
The scourge never ends’. This may be an apt description for one of the most prevalent infectious diseases-malaria. Globally, 3.3 billion people in 106 countries are at risk of malaria. In 2012, malaria caused an estimated 627,000 deaths, mostly among African children. Asia, Latin America, and to a lesser extent the Middle East and parts of Europe are also affected (WMD, 2014). Pregnant women and the under-fives form the bulk of its worst victims in endemic areas (Enatoet al., 2007).

Tackling malaria in pregnancy contributes to three of the Millennium Development Goals (MDGs), namely: goals 4 (To reduce child mortality), 5 (To improve maternal health) and 6 (To combat HIV/ AIDS, malaria and other diseases). Almost 30 million women are threatened by malaria in pregnancy (MiP) annually with about 10,000 maternal mortalities attributed to the disease each year and about 200,000 new born deaths annually (Mokuolu, 2011).

It is obvious that malaria in pregnancy causes tremendous strain on the already weakened health systems in endemic countries. The emergence of the human immunodeficiency virus (HIV) scourge has worsened the dimension of the already precarious condition. These all combined to make malaria infection a major public health problem in the tropics and subtropics(Cohen et al., 2005).

In  the  developing  world,  young  women,  pregnant  women,  their  infants  and  children frequently experience a cycle where under-nutrition (macronutrient and micronutrient) and repeated infection lead to adverse consequences that can continue from one generation to 1

the next. Infants born prematurely or with low birth weight (LBW) are at increased risk of early death or at risk of poor growth and development in childhood and adolescence (Steketeeet al., 2001). The poor growth resulting in underweight and stunting leaves reproductive-age women at risk in their early pregnancies of delivering premature or LBW infants. In addition, the micronutrient deficiencies, particularly iron and folate deficiencies (which contribute to anemia), leave the young women at risk of anemia leading to inadequate oxygen-carrying capacity and risk in pregnancy of delivering premature or LBW infants (Steketeeet al.,2006).

It was suggested that offspring of placental-infected multigravida women have the highest risk of P. falciparum during the first years of life compared to children of Primigravid placental non-infected women. Plasmodium falciparum is the only human malaria parasite with a clear and substantial adverse effect on pregnancy, nutrition during pregnancy and pregnancy outcome (Brabin, 1991). The first reaction of the body to immunological stress is the innate, non-specific response preceding specific immune reactions. The acute phase response (APR) is a prominent systemic reaction of the organism to local or systemic disturbances in its homeostasis caused by infection, tissue injury, trauma or surgery, neoplastic growth or immunological disorders (Gordon and Koy, 1985; Gruyset al., 1999).

Intensive studies of the immune response to malaria parasites in human beings have provided a wealth of information about the cells and cytokines implicated in the pathophysiology of survival and fatal outcome in severe infections. This suggests that a crucial balance might exist during the inflammatory response to malaria infection and unbalanced response leads to severe disease. In mild malaria, inflammatory response might be down regulated by anti-inflammatory cytokines, including interleukin 4, interleukin 10 and Transforming Growth Factor B (TGF-B) (Lucia and Salvatore, 2002).

The pathophysiological response to infection with Plasmodium falciparum is highly variable. It depends on several factors including previously acquired immunity and the production of cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), y-interferon (ɤ -IFN), and interleukin-6 (IL-6). Secretion of these mediators is thought to be responsible for many of the clinical features of malaria (Inigo and Manuel, 2002).

Although the stimulus to acute phase reactants production is not fully understood, macrophage derived cytokines including IL-6, TNF, and IL-1 are thought to be important (Gabay and Kushner, 1999).

Estimation of other changes in acute-phase proteins, despite the lack of diagnostic specificity, is useful to clinicians because such changes reflect the presence and intensity of an inflammatory process. Thus, measurements of plasma or serum C-reactive protein can be used to differentiate inflammatory from non-inflammatory conditions and are useful in managing the patient's disease, since the concentration often reflects the response to and the need for therapeutic intervention. In some diseases, such as rheumatoid arthritis, serial measurements of C-reactive protein are of prognostic value. Serum amyloid A concentrations usually parallel those of C-reactive protein, although some studies indicate that serum amyloid A is a more sensitive marker of inflammatory disease. At present, assays for serum amyloid A are not widely available (Gabay and Kushner, 1999).

C-reactive protein is a pentameric protein molecule which has been conserved over a long period  of  evolution.  It  binds  to  phosphorylcholine  epitopes  found  in  Streptococcus pneumoniae and many parasites, these binding results in the activation of .the classical complement pathway. Increased concentrations of C-reactive protein have also been used to distinguish acute pyogenic from viral meningitis. Serum amyloid A is the precursor of amyloid A protein found in the amyloid fibrils present in secondary amyloid deposits. Both proteins increase in concentration in the serum up to 1000 times in response to inflammatory stimuli, whether infective or traumatic. Measurement of acute phase reactants like C-reactive protein or serum amyloid A has been used to monitor the response to antibacterial treatment (Gruyset al., 2005).

1.2       Statement of Research Problem
Malaria infection (especially of Plasmodium falciparum) during pregnancy is a significant health problem with substantialrisk to the pregnant women, her fetus and new born child (WHO, 2013).

The use of cytokines for the diagnosis of malaria has been in practice for sometimes. But their short half-life in serum makes assay difficult to interpret for clinical purposes (Gabay and Kushner, 2009).

Acute phase proteins concentrations have been advocated as objective biochemical indices of disease activity in a number of different inflammatory processes. Though, it is not well documented whether parasitemia can mount a comprehensive acute phase protein response and if so, whether this is achieved by increasing acute phase protein synthesis due to the presence of malaria parasite (Yapiet al., 2010).

1.3       Justification
An emerging view is that pathogenesis of malaria is a complex process in which a common outcome might be reached by different routes. This idea emphasizes the relevance of diagnostic and prognostic parameters in predicting the specific risk associated with different clinical characteristics (Miller et al., 2002).

This study was designed to test whether measurement of acute phase reactants instead of cytokine concentration would prove valuable in the diagnosis of malaria (especially of Plasmodium falciparum) in addition to standard laboratory methods, also whether sequential measurement would be valuable in assessing response to antimalarial treatment.

Clinical studies in large groups of patients with a variety of disorders confirmed the rapid production and exceptionally wide dynamic range of the serum amyloid A (SAA) response. It is as sensitive a marker for the acute phase as C- reactive protein (CRP). Therefore, determination of APPs can be used as fact in monitoring health of individual subjects especially when several acute phase variables are combined in an index (Gruyset al., 2005).

1.4       Aim
To assess the nutritional status and some Acute Phase Proteins levels of pregnant women with Plasmodium falciparum attending three Primary Health Care centers, in Samaru Zaria.

1.4.1 Specific Objectives
i. To determine the prevalence rate of P. falciparum infection in pregnant women attending PHCs in Samaru Community.

ii. To document the socio-demographic characteristics of pregnant women with malaria (Plasmodium falciparum)and assess use of Intermittent Preventive Treatment for prevention of Malaria in Pregnancy (IPTp).

iii. To determine the relationship between malaria parasite density, parity and gestation period of pregnant mothers Infected with Plasmodium falciparum.

iv. To assess changes in indices of Iron status (Fe, Hb, serum Ferritin/ Transferrin) during Plasmodium falciparum infection in pregnancy.

v. To determine relationship between the nutritional status of pregnant women with and without Plasmodium falciparum Infection.

vi. To determine the effect of malaria parasite burden on C-reactive protein and serum amyloid A among pregnant women with parasitemia.

1.5       Null Hypothesis
There’s no relationship between Acute Phase Proteins (APP) production and malaria parasite density.

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